Protective Effects of Some Natural Products Against the Hepatotoxicity Induced by Cisplatin in Protein Malnourished Rats

Y Raslan1, E Ezzeldin2,3. 1Pharmacology Department, National Organization for Drug Control and Research, Cairo, P.O. Box 29., Egypt, 2Basic Medical Science Department and Drug Bioavailability Center, National Organization for Drug Control and Research, Cairo, P.O. Box 29., Egypt, 3Drug Bioavailability Lab. College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh11451,, Saudi Arabia

Abstract

Background. Protein malnutrition is one of the major public health problems in developing countries as consequences of economic problems. Cisplatin is an effective anticancer drug that elicits many hepatotoxicity mainly due to induction of oxidative and stresses during prolonged chemotherapy. The severity of these side effects restricts its clinical use under long term treatment.

Objective. This study was carried out to determine if fresh garlic homogenate (FGH), ginko biloba extract (GBE) or silymarin exerts a beneficial or protective effects against cisplatin induced hepatotoxicity in normally fed or protein malnourished rats.

Method. Sprague-Dawley rats weighing 250 ±30 g were divided into two sets, normally fed set (set I) and protein malnourished set (set II). Each of the two sets divided into control group and seven-treated groups. The 1st (control group) received vehicle orally (1ml/kg of 0.9 saline) on days 1 to 3, the 2nd, 3rd, 4th groups were received orally 500mg/kg, FGH, 100mg/kg, GBE and 200 mg/kg, silymarin once daily for three days respectively. The 5th group was injected intra-peritoneal (ip.) with single dose of 15mg/kg cisplatin. Groups 6th, 7th and 8th received, FGH, GBE and silymarin for 3 days followed by single dose of cisplatin 15mg/kg, i.p. on the fourth day. Twenty four hours after treatment, the animals were sacrificed, the blood was collected for biochemical analysis, and sample from livers were taken for The reactive oxygen species (ROS), antioxidant detection and histopathological examination. Statistical analysis was done by Student 't' test and one way ANOVA test.

Results . In normally fed rats, cisplatin significantly increased serum aspartate aminotransferase “AST” and serum alanine aminotransferase “ALT” levels, as well as liver body weight ratio. ROS parameters showed a significant (P<0.05) increase in malondehyde (MDA) and nitric oxide (NO) and significant (P<0.05) decrease in glutathione (GSH) and superoxide dismutase (SOD). Protein malnutrition significantly potentiate the side effects induced by cisplatin (P<0.01). Pre-treatment with FGH, GBE or silymarin before cisplatin administrations attenuate cisplatin hepatotoxicity, improve the activities of GSH and SOD and the levels of MDA (P<0.05). The histopathological lesions in liver rats administered with cisplatin were improved on using FGH, GBE and silymarin before cisplatin either with NF or PM groups.

Conclusions. Protein malnutrition potentiates cisplatin toxicity. FGH, GBE and silymarin have a partial protective effect against the cisplatin toxicity induced in normally fed and in protein malnourished rats.